title: In vivo action of IL-27: reciprocal regulation of Th17 and Treg cells in collagen-induced arthritis.
abstract: Interleukin (IL)-27 is a novel cytokine of the IL-6/IL-12 family that has been reported to be involved in the pathogenesis of autoimmune diseases and has a pivotal role as both a pro- and anti-inflammatory cytokine. We investigated the in vivo effects of IL-27 on arthritis severity in a murine collagen-induced arthritis (CIA) model and its mechanism of action regarding control of regulatory T (Tregs) and IL-17-producing T helper 17 (Th17) cells. IL-27-Fc-treated CIA mice showed a lower severity of arthritis. IL-17 expression in the spleens was significantly decreased in IL-27-Fc-treated CIA mice compared with that in the CIA model. The Th17 population was decreased in the spleens of IL-27-Fc-treated CIA mice, whereas the CD4(+)CD25(+)Foxp3(+) Treg population increased. In vitro studies revealed that IL-27 inhibited IL-17 production in murine CD4(+) T cells, and the effect was associated with retinoic acid-related orphan receptor γT and signal transducer and activator of transcription 3 inhibition. In contrast, fluorescein isothiocyanate-labeled forkhead box P3 (Foxp3) and IL-10 were profoundly augmented by IL-27 treatment. Regarding the suppressive capacity of Treg cells, the proportions of CTLA-4(+) (cytotoxic T-lymphocyte antigen 4), PD-1(+) (programmed cell death protein 1) and GITR(+) (glucocorticoid-induced tumor necrosis factor receptor) Tregs increased in the spleens of IL-27-Fc-treated CIA mice. Furthermore, in vitro differentiated Treg cells with IL-27 exerted a more suppressive capacity on T-cell proliferation. We found that IL-27 acts as a reciprocal regulator of the Th17 and Treg populations in CD4(+) cells isolated from healthy human peripheral blood mononuclear cells (PBMCs), as well as from humans with rheumatoid arthritis (RA) PBMCs. Our study suggests that IL-27 has the potential to ameliorate overwhelming inflammation in patients with RA through a reciprocal regulation of Th17 and Treg cells.
authors.affiliation: Bucheon St Mary's Hospital, Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Bucheon City, Gyeonggi-do, Republic of Korea.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Moon
authors.forename: Jin-Sil
authors.initials: JS
authors.lastname: Park
authors.forename: Yu-Jung
authors.initials: YJ
authors.lastname: Heo
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Kang
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.forename: Mi-Ae
authors.initials: MA
authors.lastname: Lim
authors.forename: Jun-Geol
authors.initials: JG
authors.lastname: Ryu
authors.forename: Seong Jeong
authors.initials: SJ
authors.lastname: Park
authors.forename: Kyung Su
authors.initials: KS
authors.lastname: Park
authors.forename: Young-Chul
authors.initials: YC
authors.lastname: Sung
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.forename: Ho-Youn
authors.initials: HY
authors.lastname: Kim
authors.forename: Jun-Ki
authors.initials: JK
authors.lastname: Min
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007378:Interleukins / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: C486767:Il27 protein, mouse; D007378:Interleukins